Transcriptional Regulation of the Processes of Human Labour and Delivery
Transcriptional Regulation of the Processes of Human Labour and Delivery
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DOI：
10.1016/j.placenta.2008.10.005
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发表时间：
2009-03-01
期刊：
影响因子：
3.8
通讯作者：
Rice, G. E.
中科院分区：
文献类型：
--
作者：
Lappas, M.;Rice, G. E.
早产是导致不良妊娠和新生儿结局的最重要的并发症。必须解决的一个关键问题是如何在足月和早产时启动自然临产。在过去的十年里，我们和其他人已经提供了证据来支持这一假说，即临产是由特定的核调节因子(NR)途径调控的，涉及转录因子(TF)和核激素受体之间的相互作用，这些途径控制着许多分娩和分娩所必需的效应器途径的表达。现在有令人信服的证据表明NRS，包括核因子-kappa B(核因子-kappa B)家族的核转录因子。核激素受体超家族的过氧化物酶体增殖物激活受体(PPAR)和孕酮的类固醇受体(PRA、PRB和PRC)被认为是与分娩相关的过程的候选上游调节因子。基于这些研究和我们实验室获得的最新数据，我们提供了一个新的模型，说明在自然分娩和分娩过程中涉及的多个途径是如何在核水平上协调的。我们认为，自然分娩和分娩是由于核受体(PPAR和PR)对促分娩因子途径(NF-kappa B)的抑制作用消失所致。NR介导的抑制作用的撤销受到转录因子和转录因子对有限的核辅因子的竞争的影响。我们还提出，这些不同途径的协调是通过竞争控制人类妊娠组织中NRs活性的共同辅助因子来实现的。(C)2009年，由IFPA和爱思唯尔有限公司出版。
Preterm birth is the most important complication contributing to poor pregnancy and neonatal outcome. A critical issue that must be resolved is how spontaneous onset labour is initiated both at term and preterm. Over the past decade, we and others have provided evidence in support of the hypothesis that labour onset is regulated by specific nuclear regulatory factor (NR) pathways, involving an interplay between transcription factors (TFs) and nuclear hormone receptors, that control the expression of many of the effector pathways requisite for labour and delivery. There is now compelling evidence implicating NRs, including the nuclear factor-kappa B (NF-kappa B) family of nuclear TFs. the nuclear hormone receptor superfamily of peroxisome proliferator activated receptors (PPARs), and the steroid receptors for progesterone (PRA, PRB and PRC), as candidate upstream regulators of labour-associated processes. Based on these studies and recent data obtained in our laboratory, we provide a new model of how the multiple pathways involved in spontaneous onset labour and delivery are coordinated at a nuclear level. We propose that spontaneous onset labour and delivery are consequent upon withdrawal of the repressive effect of nuclear receptors (PPAR and PR) on pro-labour TF pathways (NF-kappa B). The withdrawal of NR-mediated repression is affected by competition between TFs and NRs for a limited pool of nuclear cofactors. We also propose that coordination of these different pathways is achieved by competition for common cofactors that control the activity of NRs in human gestational tissues. (C) 2009 Published by IFPA and Elsevier Ltd.